Dear Editor,In 2019,a zoonotic coronavirus named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was identified as the causative agent of Coronavirus Disease 2019(COVID-19).As of 8 June 2020,the World Healt...Dear Editor,In 2019,a zoonotic coronavirus named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was identified as the causative agent of Coronavirus Disease 2019(COVID-19).As of 8 June 2020,the World Health Organization(WHO)has reported 6,912,751 globally confirmed cases with 400,469 deaths.Although generally causes mild disease,SARS-CoV-2 infection can result in serious outcomes,including acute lung injury(ALI)and acute respiratory distress syndrome(ARDS),the leading cause of mortality in patients with comorbidities.Recent autopsy studies of COVID-19 patients revealed mononuclear infiltration and excessive production of mucus in the infected lung,especially in the damaged small airways and alveoli(Bian and Team,2020;Liu et al.,2020).展开更多
Background Metabolism reprogramming plays a vital role in glioblastoma(GBM)progression and recurrence by producing enough energy for highly proliferating tumor cells.In addition,metabolic reprogramming is crucial for ...Background Metabolism reprogramming plays a vital role in glioblastoma(GBM)progression and recurrence by producing enough energy for highly proliferating tumor cells.In addition,metabolic reprogramming is crucial for tumor growth and immune-escape mechanisms.Epidermal growth factor receptor(EGFR)amplification and EGFR-vIII mutation are often detected in GBM cells,contributing to the malignant behavior.This study aimed to investigate the functional role of the EGFR pathway on fatty acid metabolism remodeling and energy generation.Methods Clinical GBM specimens were selected for single-cell RNA sequencing and untargeted metabolomics analysis.A metabolism-associated RTK-fatty acid-gene signature was constructed and verified.MK-2206 and MK-803 were utilized to block the RTK pathway and mevalonate pathway induced abnormal metabolism.Energy metabolism in GBM with activated EGFR pathway was monitored.The antitumor effect of Osimertinib and Atorvastatin assisted by temozolomide(TMZ)was analyzed by an intracranial tumor model in vivo.Results GBM with high EGFR expression had characteristics of lipid remodeling and maintaining high cholesterol levels,supported by the single-cell RNA sequencing and metabolomics of clinical GBM samples.Inhibition of the EGFR/AKT and mevalonate pathways could remodel energy metabolism by repressing the tricarboxylic acid cycle and modulating ATP production.Mechanistically,the EGFR/AKT pathway upregulated the expressions of acyl-CoA synthetase short-chain family member 3(ACSS3),acyl-CoA synthetase long-chain family member 3(ACSL3),and long-chain fatty acid elongation-related gene ELOVL fatty acid elongase 2(ELOVL2)in an NF-κB-dependent manner.Moreover,inhibition of the mevalonate pathway reduced the EGFR level on the cell membranes,thereby affecting the signal transduction of the EGFR/AKT pathway.Therefore,targeting the EGFR/AKT and mevalonate pathways enhanced the antitumor effect of TMZ in GBM cells and animal models.Conclusions Our findings not only uncovered the mechanism of metabolic rep展开更多
When new information enters the brain,a human's prior knowledge of the world can change rapidly through a process referred to as"knowledge assembly".Recently,Nelli et al.investigated the neural correlate...When new information enters the brain,a human's prior knowledge of the world can change rapidly through a process referred to as"knowledge assembly".Recently,Nelli et al.investigated the neural correlates of knowledge assembly in the human brain using functional MRI.Further,inspired by the neural mechanism,the authors developed an artificial neural network algorithm to permit rapid knowledge assembly,improving the flexibility of the system[1].Once again,this research demonstrates that studying how the brain works can lead to better computational algorithms.展开更多
Background PTPRZ1-MET fusion was reported to associate with glioma progression from low-grade to high-grade glioma,which was a target by a MET inhibitor vebreltinib.However,little is known about the further efficacy o...Background PTPRZ1-MET fusion was reported to associate with glioma progression from low-grade to high-grade glioma,which was a target by a MET inhibitor vebreltinib.However,little is known about the further efficacy of vebreltinib among more glioma patients.This trial aims to evaluate the safety and efficacy of vebreltinib enteric-coated capsules in the treatment of sGBM/IDH mutant glioblastoma patients with the ZM fusion gene.Methods This multicentric,randomized,open-label,controlled trial plans to include 19 neurosurgical centers and recruit 84 sGBM or IDH mutant glioblastoma patients with the ZM fusion gene.This trial enrolls sGBM or IDH mutant glioblastoma patients with the inclusion criteria and without the exclusion criteria.It was registered with chinadrugtrials.org.cn(CTR20181664).The primary efficacy endpoint is overall survival(OS).The secondary endpoints are progression-free survival(PFS)and objective response rate(ORR).Discussion If proven effective,this targeted multifaceted intervention protocol will be extended for more glioma patients as a protocol to evaluate the safety and efficacy of MET inhibitors.Trial registration It was registered with chinadrugtrials.org.cn(CTR20181664).展开更多
Background:Adjuvant temozolomide(TMZ)chemotherapy with standard regimen remarkably improves survival in patients with high-grade glioma(HGG).However,the influence of long-term TMZ chemotherapy on serum ions concentrat...Background:Adjuvant temozolomide(TMZ)chemotherapy with standard regimen remarkably improves survival in patients with high-grade glioma(HGG).However,the influence of long-term TMZ chemotherapy on serum ions concentration is unclear.Methods:One hundred and thirty-eight patients with HGG were included.Their blood samples were collected for blood biochemistry and routine test.The alteration in serum ions concentration,total protein,albumin,globin,and blood cells counts were used to identify the impact of long-term TMZ chemotherapy.Results:Through the comparation of quantitative value of diverse parameters among different chemotherapy cycles,we identified that serum potassium concentration had a downward trend after TMZ administration(1st vs.6th,p<0.001;1st vs.12th,p<0.001).Additionally,the correlation analysis showed that platelets was negatively correlated with chemotherapy cycles(r=−0.649,p=0.023).The hematological adverse events mainly centered on grade 1 to 2.Conclusion:Long-term administration of TMZ may lead to serum ions disturbance.Besides the myelosuppression,we should pay attention to the alteration in serum ions concentration,and give patients proper symptomatic treatment when necessary.展开更多
Central to the core principle of cell theory,depicting cells'history,state and fate is a fundamental goal in modern biology.By leveraging clonal analysis and sin-gle-cell RNA-seq technologies,single-cell lineage t...Central to the core principle of cell theory,depicting cells'history,state and fate is a fundamental goal in modern biology.By leveraging clonal analysis and sin-gle-cell RNA-seq technologies,single-cell lineage trac-ing provides new opportunities to interrogate both cell states and lineage histories.During the past few years,many strategies to achieve lineage tracing at single-cell resolution have been developed,and three of them(in-tegration barcodes,polylox barcodes,and CRISPR barcodes)are noteworthy as they are amenable in experimentally tractable systems.Although the above strategies have been demonstrated in animal develop-ment and stem cell research,much care and effort are still required to implement these methods.Here we review the development of single-cell lineage tracing,major characteristics of the cell barcoding strategies,applications,as well as technical considerations and limitations,providing a guide to choose or improve the single-cell barcoding lineage tracing.展开更多
Polycyclic aromatic hydrocarbons(PAHs)are promising nanocarbon materials with diverse optoelectronic properties,yet they also pose concerning environmental and health risks.Despite the ubiquity of PAHs in the environm...Polycyclic aromatic hydrocarbons(PAHs)are promising nanocarbon materials with diverse optoelectronic properties,yet they also pose concerning environmental and health risks.Despite the ubiquity of PAHs in the environment(crude oil,emissions,and biomass),most supermolecules rely on heteroatoms for stability.We discovered and characterized a family of all-hydrocarbon,all-π-conjugated[n]cycloparaphenylene-PAH host–guest complexes.We built a theoretical framework to rapidly select these complexes and predict their stabilities,driven exclusively by CH–πinteractions.More than a dozen complexes were confirmed experimentally and assembled directly from commercially available compounds.This motif offers a versatile way to combine the advantageous properties of organic semiconductors with the rich dynamic,stereochemical,stimulus-responsive,and stressdissipative behavior of host–guest complexes,while creating new opportunities for bespoke PAH separation or remediation materials.展开更多
BACKGROUND Mesenchymal stromal cell(MSC)-based cellular therapy promotes type I collagen production,enhance mechanical strength of tissues,and enhance biology at the bone-tendon interface,which primarily explains thei...BACKGROUND Mesenchymal stromal cell(MSC)-based cellular therapy promotes type I collagen production,enhance mechanical strength of tissues,and enhance biology at the bone-tendon interface,which primarily explains their potential clinical utility in rotator cuff(RC)tears.AIM To analyze the efficacy and safety of cellular therapy utilizing MSCs in the management of RC tears from clinical studies available in the literature.METHODS We conducted independent and duplicate electronic database searches including PubMed,Embase,Reference Citation Anallysis,Web of Science,and Cochrane Library in August 2021 for studies analyzing the efficacy and safety of cellular therapy(CT)utilizing MSCs in the management of RC tears.Visual Analog Score(VAS)score for pain,American Shoulder and Elbow Surgeons(ASES)score,Disability of the Arm,Shoulder,and Hand score,Constant score,radiological assessment of healing,and complications such as retear rate and adverse events were the outcomes analyzed.Analysis was performed in R-platform using OpenMeta[Analyst]software.RESULTS Six studies involving 238 patients were included for analysis.We noted a significant reduction in VAS score for pain at 3 mo(weighed mean difference[WMD]=-2.234,P<0.001)and 6 mo(WMD=-3.078,P<0.001)with the use of CT,which was not maintained at long-term follow-up(WMD=-0.749,P=0.544).Concerning functional outcomes,utilization of CT produced a significant shortterm improvement in the ASES score(WMD=17.090,P<0.001)and significant benefit in functional scores such as Constant score(WMD=0.833,P=0.760)at long-term follow-up.Moreover,we also observed significantly improved radiological tendon healing during the longterm follow-up(odds ratio[OR]=3.252,P=0.059).We also noted a significant reduction in the retear rate upon utilization of CT in RC tears both at short-(OR=0.079,P=0.032)and long-term(OR=0.434,P=0.027)follow-ups.We did not observe any significant increase in the adverse events directly related to cellular therapy,as compared with the control group(OR=0.876,P=0.869).CO展开更多
Background:Substantial research is underway to develop next-generation interventions that address current malaria control challenges.As there is limited testing in their early development,it is difficult to predefine ...Background:Substantial research is underway to develop next-generation interventions that address current malaria control challenges.As there is limited testing in their early development,it is difficult to predefine intervention properties such as efficacy that achieve target health goals,and therefore challenging to prioritize selection of novel candidate interventions.Here,we present a quantitative approach to guide intervention development using mathematical models of malaria dynamics coupled with machine learning.Our analysis identifies requirements of efficacy,coverage,and duration of effect for five novel malaria interventions to achieve targeted reductions in malaria prevalence.Methods:A mathematical model of malaria transmission dynamics is used to simulate deployment and predict potential impact of new malaria interventions by considering operational,health-system,population,and disease characteristics.Our method relies on consultation with product development stakeholders to define the putative space of novel intervention specifications.We couple the disease model with machine learning to search this multi-dimensional space and efficiently identify optimal intervention properties that achieve specified health goals.Results:We apply our approach to five malaria interventions under development.Aiming for malaria prevalence reduction,we identify and quantify key determinants of intervention impact along with their minimal properties required to achieve the desired health goals.While coverage is generally identified as the largest driver of impact,higher efficacy,longer protection duration or multiple deployments per year are needed to increase prevalence reduction.We show that interventions on multiple parasite or vector targets,as well as combinations the new interventions with drug treatment,lead to significant burden reductions and lower efficacy or duration requirements.Conclusions:Our approach uses disease dynamic models and machine learning to support decision-making and resource investment,facilita展开更多
BACKGROUND Platelet-rich plasma has been gaining popularity as an agent for biological augmentation either as the sole treatment modality or as an adjunct to surgical repair.There is substantial discrepancy in the res...BACKGROUND Platelet-rich plasma has been gaining popularity as an agent for biological augmentation either as the sole treatment modality or as an adjunct to surgical repair.There is substantial discrepancy in the results of the published meta-analyses;and the true efficacy and role of using autologous platelet-rich plasma(PRP)at the time of rotator cuff repair is still ambiguous.AIM To performed this systematic overview on the overlapping meta-analyses that analyzed autologous PRP as an adjuvant in the repair of rotator cuff tears and identify the studies which provide the current best evidence on this subject and generate recommendations for the same.METHODS We conducted independent and duplicate electronic database searches in PubMed,Web of Science,Scopus,Embase,Cochrane Database of Systematic Reviews,Reference Citation Analysis and the Database of Abstracts of Reviews of Effects on September 8,2021 to identify meta-analyses that analyzed the efficacy of PRP as an adjuvant in the repair of rotator cuff tears.Methodological quality assessment was made using Oxford Levels of Evidence,AMSTAR scoring and AMSTAR 2 grades.We then utilized the Jadad decision algorithm to identify the study with the highest quality to represent the current best evidence to generate the recommendation.RESULTS Twenty meta-analyses fulfilling the eligibility criteria were included.The AMSTAR scores of the included studies varied from 6-10(mean:7.9).All the included studies had critically low reliability in their summary of results due to their methodological flaws according to AMSTAR 2 grades.Significant heterogeneity was observed in the reporting of VAS,function outcome scores(longterm UCLA score,ASES score,SST score),operative time and long-term re-tear rates.Recent metaanalyses are more supportive of the role of intra-operative administration of PRPs at the bonetendon interface in improving the overall healing and re-tear rates,functional outcome and pain.The initial size of the tear and type of repair performed do not seem to affect 展开更多
The global outbreak of coronavirus disease 2019(COVID-19),which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),as of 8 May 2021,has surpassed 150700000 infections and 3279000 deaths worldwide...The global outbreak of coronavirus disease 2019(COVID-19),which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),as of 8 May 2021,has surpassed 150700000 infections and 3279000 deaths worldwide.Evidence indicates that SARS-CoV-2 RNA can be detected on particulate matter(PM),and COVID-19 cases are correlated with levels of air pollutants.However,the mechanisms of PM involvement in the spread of SARS-CoV-2 remain poorly understood.Here,we found that PM exposure increased the expression level of angiotensin-converting enzyme 2(ACE2)and transmembrane serine protease 2(TMPRSS2)in several epithelial cells and increased the adsorption of the SARS-CoV-2 spike protein.Instillation of PM in a hACE2 mouse model significantly increased the expression of ACE2 and Tmprss2 and viral replication in the lungs.Furthermore,PM exacerbated the pulmonary lesions caused by SARS-CoV-2 infection in the hACE2 mice.In conclusion,our study demonstrated that PM is an epidemiological factor of COVID-19,emphasizing the necessity of wearing anti-PM masks to cope with this global pandemic.展开更多
Integrating the advantages of Bi and Cr elements in the bandgap engineering of metal oxides, a visible-light-responsive photocatalyst Bi1.5Cr0.5WO6 is successfully constructed and initially applied in water decontamin...Integrating the advantages of Bi and Cr elements in the bandgap engineering of metal oxides, a visible-light-responsive photocatalyst Bi1.5Cr0.5WO6 is successfully constructed and initially applied in water decontamination. The combination of UV-vis diffuses reflectance and the Mott-Schottky curve from electrochemical testing can be used to determine the conduction band and valence band of Bi1.5Cr0.5WO6 to be about –1.26 and 1.42 V, respectively. The location of energy band structure indicates that the superoxide free radical can be produced in Bi1.5Cr0.5WO6 photocatalytic system without hydroxyl group. This speculation is also confirmed by ESR experiment and active radical species scavenging experiments. In addition, the best photocatalytic performance of Bi1.5Cr0.5WO6 obtained under 180 ℃ is attributed to the smallest impedance and the strongest electronic migration capability.展开更多
文摘Dear Editor,In 2019,a zoonotic coronavirus named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was identified as the causative agent of Coronavirus Disease 2019(COVID-19).As of 8 June 2020,the World Health Organization(WHO)has reported 6,912,751 globally confirmed cases with 400,469 deaths.Although generally causes mild disease,SARS-CoV-2 infection can result in serious outcomes,including acute lung injury(ALI)and acute respiratory distress syndrome(ARDS),the leading cause of mortality in patients with comorbidities.Recent autopsy studies of COVID-19 patients revealed mononuclear infiltration and excessive production of mucus in the infected lung,especially in the damaged small airways and alveoli(Bian and Team,2020;Liu et al.,2020).
基金supported by grants from the National Natural Science Foundation of China(82002657,82073322,81761168038)the Hebei Natural Science Foundation Precision Medicine Joint Project(H2020201206)+4 种基金the Tianjin Key R&D Plan of Tianjin Science and Technology Plan Project(20YFZCSY00360)Brain Tumor Precision Diagnosis and Treatment and Translational Medicine Innovation Unit,Chinese Academy of Medical Sciences(2019-I2M-5-021)the Science and Technology Project of Tianjin Municipal Health Commission(TJWJ2021QN003)Key-Area Research and Development Program of Guangdong Province(2023B1111020008)Multi-input Project by Natural Science Foundation of Tianjin Municipal Science and Technology Commission(21JCQNJC01250)。
文摘Background Metabolism reprogramming plays a vital role in glioblastoma(GBM)progression and recurrence by producing enough energy for highly proliferating tumor cells.In addition,metabolic reprogramming is crucial for tumor growth and immune-escape mechanisms.Epidermal growth factor receptor(EGFR)amplification and EGFR-vIII mutation are often detected in GBM cells,contributing to the malignant behavior.This study aimed to investigate the functional role of the EGFR pathway on fatty acid metabolism remodeling and energy generation.Methods Clinical GBM specimens were selected for single-cell RNA sequencing and untargeted metabolomics analysis.A metabolism-associated RTK-fatty acid-gene signature was constructed and verified.MK-2206 and MK-803 were utilized to block the RTK pathway and mevalonate pathway induced abnormal metabolism.Energy metabolism in GBM with activated EGFR pathway was monitored.The antitumor effect of Osimertinib and Atorvastatin assisted by temozolomide(TMZ)was analyzed by an intracranial tumor model in vivo.Results GBM with high EGFR expression had characteristics of lipid remodeling and maintaining high cholesterol levels,supported by the single-cell RNA sequencing and metabolomics of clinical GBM samples.Inhibition of the EGFR/AKT and mevalonate pathways could remodel energy metabolism by repressing the tricarboxylic acid cycle and modulating ATP production.Mechanistically,the EGFR/AKT pathway upregulated the expressions of acyl-CoA synthetase short-chain family member 3(ACSS3),acyl-CoA synthetase long-chain family member 3(ACSL3),and long-chain fatty acid elongation-related gene ELOVL fatty acid elongase 2(ELOVL2)in an NF-κB-dependent manner.Moreover,inhibition of the mevalonate pathway reduced the EGFR level on the cell membranes,thereby affecting the signal transduction of the EGFR/AKT pathway.Therefore,targeting the EGFR/AKT and mevalonate pathways enhanced the antitumor effect of TMZ in GBM cells and animal models.Conclusions Our findings not only uncovered the mechanism of metabolic rep
基金supported by STI2030-Major Projects 2021ZD0200201the Scientific Research and Equipment Development Project of the Chinese Academy of Sciences(YJKYYQ20190040)。
文摘When new information enters the brain,a human's prior knowledge of the world can change rapidly through a process referred to as"knowledge assembly".Recently,Nelli et al.investigated the neural correlates of knowledge assembly in the human brain using functional MRI.Further,inspired by the neural mechanism,the authors developed an artificial neural network algorithm to permit rapid knowledge assembly,improving the flexibility of the system[1].Once again,this research demonstrates that studying how the brain works can lead to better computational algorithms.
基金funded by The National Key Research and Development Program of China(2019YFE0109400)National Natural Science Foundation of China(No.81972337 and No.81802994)+1 种基金Beijing Natural Science Foundation(No.JQ20030)Outstanding Young Talents of the Capital Medical University(No.B2101)
文摘Background PTPRZ1-MET fusion was reported to associate with glioma progression from low-grade to high-grade glioma,which was a target by a MET inhibitor vebreltinib.However,little is known about the further efficacy of vebreltinib among more glioma patients.This trial aims to evaluate the safety and efficacy of vebreltinib enteric-coated capsules in the treatment of sGBM/IDH mutant glioblastoma patients with the ZM fusion gene.Methods This multicentric,randomized,open-label,controlled trial plans to include 19 neurosurgical centers and recruit 84 sGBM or IDH mutant glioblastoma patients with the ZM fusion gene.This trial enrolls sGBM or IDH mutant glioblastoma patients with the inclusion criteria and without the exclusion criteria.It was registered with chinadrugtrials.org.cn(CTR20181664).The primary efficacy endpoint is overall survival(OS).The secondary endpoints are progression-free survival(PFS)and objective response rate(ORR).Discussion If proven effective,this targeted multifaceted intervention protocol will be extended for more glioma patients as a protocol to evaluate the safety and efficacy of MET inhibitors.Trial registration It was registered with chinadrugtrials.org.cn(CTR20181664).
基金This work was supported by funding from the National Key Research and Development Plan(No. 2016YFC0902500)the National Natural Science Foundation of China(No. 81903060)the Cultivation Plan of Beijing Hospital Management Center(PX2021025)
文摘Background:Adjuvant temozolomide(TMZ)chemotherapy with standard regimen remarkably improves survival in patients with high-grade glioma(HGG).However,the influence of long-term TMZ chemotherapy on serum ions concentration is unclear.Methods:One hundred and thirty-eight patients with HGG were included.Their blood samples were collected for blood biochemistry and routine test.The alteration in serum ions concentration,total protein,albumin,globin,and blood cells counts were used to identify the impact of long-term TMZ chemotherapy.Results:Through the comparation of quantitative value of diverse parameters among different chemotherapy cycles,we identified that serum potassium concentration had a downward trend after TMZ administration(1st vs.6th,p<0.001;1st vs.12th,p<0.001).Additionally,the correlation analysis showed that platelets was negatively correlated with chemotherapy cycles(r=−0.649,p=0.023).The hematological adverse events mainly centered on grade 1 to 2.Conclusion:Long-term administration of TMZ may lead to serum ions disturbance.Besides the myelosuppression,we should pay attention to the alteration in serum ions concentration,and give patients proper symptomatic treatment when necessary.
基金supported in part by National Key R&D Program of China(2018YFA0801402,2018YFA0107200)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16020404)+3 种基金Guangdong Basic and Applied Basic Research Foundation(2019B151502054)Frontier Research Program of Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory,2018GZR110105013)Jiazi Research Innovative Project of Bioland Laboratory(2019GZR110108001)Science and Technology Planning Project of Guangdong Province(2020B1212060052).
文摘Central to the core principle of cell theory,depicting cells'history,state and fate is a fundamental goal in modern biology.By leveraging clonal analysis and sin-gle-cell RNA-seq technologies,single-cell lineage trac-ing provides new opportunities to interrogate both cell states and lineage histories.During the past few years,many strategies to achieve lineage tracing at single-cell resolution have been developed,and three of them(in-tegration barcodes,polylox barcodes,and CRISPR barcodes)are noteworthy as they are amenable in experimentally tractable systems.Although the above strategies have been demonstrated in animal develop-ment and stem cell research,much care and effort are still required to implement these methods.Here we review the development of single-cell lineage tracing,major characteristics of the cell barcoding strategies,applications,as well as technical considerations and limitations,providing a guide to choose or improve the single-cell barcoding lineage tracing.
基金supported by the American Chemical Society Petroleum Research Fund Doctoral New Investigator grant(No.59067-DNI7)Further support was provided by the College of Engineering and Applied Science at the University of Colorado Boulder.This work utilized resources from the University of Colorado Boulder Research Computing Group,which is supported by the National Science Foundation(awards ACI-1532235 and ACI-1532236)the University of Colorado Boulder,and Colorado State University.
文摘Polycyclic aromatic hydrocarbons(PAHs)are promising nanocarbon materials with diverse optoelectronic properties,yet they also pose concerning environmental and health risks.Despite the ubiquity of PAHs in the environment(crude oil,emissions,and biomass),most supermolecules rely on heteroatoms for stability.We discovered and characterized a family of all-hydrocarbon,all-π-conjugated[n]cycloparaphenylene-PAH host–guest complexes.We built a theoretical framework to rapidly select these complexes and predict their stabilities,driven exclusively by CH–πinteractions.More than a dozen complexes were confirmed experimentally and assembled directly from commercially available compounds.This motif offers a versatile way to combine the advantageous properties of organic semiconductors with the rich dynamic,stereochemical,stimulus-responsive,and stressdissipative behavior of host–guest complexes,while creating new opportunities for bespoke PAH separation or remediation materials.
文摘BACKGROUND Mesenchymal stromal cell(MSC)-based cellular therapy promotes type I collagen production,enhance mechanical strength of tissues,and enhance biology at the bone-tendon interface,which primarily explains their potential clinical utility in rotator cuff(RC)tears.AIM To analyze the efficacy and safety of cellular therapy utilizing MSCs in the management of RC tears from clinical studies available in the literature.METHODS We conducted independent and duplicate electronic database searches including PubMed,Embase,Reference Citation Anallysis,Web of Science,and Cochrane Library in August 2021 for studies analyzing the efficacy and safety of cellular therapy(CT)utilizing MSCs in the management of RC tears.Visual Analog Score(VAS)score for pain,American Shoulder and Elbow Surgeons(ASES)score,Disability of the Arm,Shoulder,and Hand score,Constant score,radiological assessment of healing,and complications such as retear rate and adverse events were the outcomes analyzed.Analysis was performed in R-platform using OpenMeta[Analyst]software.RESULTS Six studies involving 238 patients were included for analysis.We noted a significant reduction in VAS score for pain at 3 mo(weighed mean difference[WMD]=-2.234,P<0.001)and 6 mo(WMD=-3.078,P<0.001)with the use of CT,which was not maintained at long-term follow-up(WMD=-0.749,P=0.544).Concerning functional outcomes,utilization of CT produced a significant shortterm improvement in the ASES score(WMD=17.090,P<0.001)and significant benefit in functional scores such as Constant score(WMD=0.833,P=0.760)at long-term follow-up.Moreover,we also observed significantly improved radiological tendon healing during the longterm follow-up(odds ratio[OR]=3.252,P=0.059).We also noted a significant reduction in the retear rate upon utilization of CT in RC tears both at short-(OR=0.079,P=0.032)and long-term(OR=0.434,P=0.027)follow-ups.We did not observe any significant increase in the adverse events directly related to cellular therapy,as compared with the control group(OR=0.876,P=0.869).CO
基金This work was supported by the Bill&Melinda Gates Foundation(OPP1170505 to MAP)the Swiss National Science Foundation(PP00P3_170702 to MAP).
文摘Background:Substantial research is underway to develop next-generation interventions that address current malaria control challenges.As there is limited testing in their early development,it is difficult to predefine intervention properties such as efficacy that achieve target health goals,and therefore challenging to prioritize selection of novel candidate interventions.Here,we present a quantitative approach to guide intervention development using mathematical models of malaria dynamics coupled with machine learning.Our analysis identifies requirements of efficacy,coverage,and duration of effect for five novel malaria interventions to achieve targeted reductions in malaria prevalence.Methods:A mathematical model of malaria transmission dynamics is used to simulate deployment and predict potential impact of new malaria interventions by considering operational,health-system,population,and disease characteristics.Our method relies on consultation with product development stakeholders to define the putative space of novel intervention specifications.We couple the disease model with machine learning to search this multi-dimensional space and efficiently identify optimal intervention properties that achieve specified health goals.Results:We apply our approach to five malaria interventions under development.Aiming for malaria prevalence reduction,we identify and quantify key determinants of intervention impact along with their minimal properties required to achieve the desired health goals.While coverage is generally identified as the largest driver of impact,higher efficacy,longer protection duration or multiple deployments per year are needed to increase prevalence reduction.We show that interventions on multiple parasite or vector targets,as well as combinations the new interventions with drug treatment,lead to significant burden reductions and lower efficacy or duration requirements.Conclusions:Our approach uses disease dynamic models and machine learning to support decision-making and resource investment,facilita
文摘BACKGROUND Platelet-rich plasma has been gaining popularity as an agent for biological augmentation either as the sole treatment modality or as an adjunct to surgical repair.There is substantial discrepancy in the results of the published meta-analyses;and the true efficacy and role of using autologous platelet-rich plasma(PRP)at the time of rotator cuff repair is still ambiguous.AIM To performed this systematic overview on the overlapping meta-analyses that analyzed autologous PRP as an adjuvant in the repair of rotator cuff tears and identify the studies which provide the current best evidence on this subject and generate recommendations for the same.METHODS We conducted independent and duplicate electronic database searches in PubMed,Web of Science,Scopus,Embase,Cochrane Database of Systematic Reviews,Reference Citation Analysis and the Database of Abstracts of Reviews of Effects on September 8,2021 to identify meta-analyses that analyzed the efficacy of PRP as an adjuvant in the repair of rotator cuff tears.Methodological quality assessment was made using Oxford Levels of Evidence,AMSTAR scoring and AMSTAR 2 grades.We then utilized the Jadad decision algorithm to identify the study with the highest quality to represent the current best evidence to generate the recommendation.RESULTS Twenty meta-analyses fulfilling the eligibility criteria were included.The AMSTAR scores of the included studies varied from 6-10(mean:7.9).All the included studies had critically low reliability in their summary of results due to their methodological flaws according to AMSTAR 2 grades.Significant heterogeneity was observed in the reporting of VAS,function outcome scores(longterm UCLA score,ASES score,SST score),operative time and long-term re-tear rates.Recent metaanalyses are more supportive of the role of intra-operative administration of PRPs at the bonetendon interface in improving the overall healing and re-tear rates,functional outcome and pain.The initial size of the tear and type of repair performed do not seem to affect
基金This work was supported by the National Natural Science Foundation of China(NSFC)(31900331,32070444)Science and Technology Department of Yunnan Province(202001AW070019)+2 种基金Chinese Academy of Sciences“Light of West China”Program and Youth Innovation Promotion Association(2019378)to L.J.and the NSFC(21761142002)Chinese Academy of Sciences(XDB31000000,SAJC201606 and KGFZD-135-17-011)Yunnan Province(2019-YT-053 and 2019ZF003)to R.L.and the NSFC(91643206)to W.J.D。
文摘The global outbreak of coronavirus disease 2019(COVID-19),which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),as of 8 May 2021,has surpassed 150700000 infections and 3279000 deaths worldwide.Evidence indicates that SARS-CoV-2 RNA can be detected on particulate matter(PM),and COVID-19 cases are correlated with levels of air pollutants.However,the mechanisms of PM involvement in the spread of SARS-CoV-2 remain poorly understood.Here,we found that PM exposure increased the expression level of angiotensin-converting enzyme 2(ACE2)and transmembrane serine protease 2(TMPRSS2)in several epithelial cells and increased the adsorption of the SARS-CoV-2 spike protein.Instillation of PM in a hACE2 mouse model significantly increased the expression of ACE2 and Tmprss2 and viral replication in the lungs.Furthermore,PM exacerbated the pulmonary lesions caused by SARS-CoV-2 infection in the hACE2 mice.In conclusion,our study demonstrated that PM is an epidemiological factor of COVID-19,emphasizing the necessity of wearing anti-PM masks to cope with this global pandemic.
基金financially supported by the Natural Science Foundation of Fujian province(2016J05042,2015J01057,2018J01439)Open Fund of State Key Laboratory of Photocatalysis on Energy and Environment(SKLPEE-KF201505)+3 种基金Scientific Project of Putian Science and Technology Bureau(2016S1001)Science and Technology Project of Fujian Provincial Department of Education(JA15444)the Projects of Putian University(2015065,2015081)Program for New Century Excellent Talents in Fujian Province University
文摘Integrating the advantages of Bi and Cr elements in the bandgap engineering of metal oxides, a visible-light-responsive photocatalyst Bi1.5Cr0.5WO6 is successfully constructed and initially applied in water decontamination. The combination of UV-vis diffuses reflectance and the Mott-Schottky curve from electrochemical testing can be used to determine the conduction band and valence band of Bi1.5Cr0.5WO6 to be about –1.26 and 1.42 V, respectively. The location of energy band structure indicates that the superoxide free radical can be produced in Bi1.5Cr0.5WO6 photocatalytic system without hydroxyl group. This speculation is also confirmed by ESR experiment and active radical species scavenging experiments. In addition, the best photocatalytic performance of Bi1.5Cr0.5WO6 obtained under 180 ℃ is attributed to the smallest impedance and the strongest electronic migration capability.
